Structure-Function Relationships in Assembly of the Radical-Initiating Cofactors of Class Ia–e Ribonucleotide Reductases

Class I ribonucleotide reductases (RNRs) are composed of a catalytic α subunit and a cofactor-containing β subunit. In well-characterized class I RNRs, the β subunits bind iron (II) and/or manganese(II), then react with oxygen or superoxide to assemble the active subunit with its oxidized dinuclear metal cluster. The activated metallocofactor in the β subunit transfers a required oxidizing equivalent to the α subunit to initiate ribonucleotide reduction therein. Here we compare the structures of the β subunits in each of the five known subclasses of class I RNR—including the newly discovered manganese-dependent class Id and metal-free class Ie systems. This chapter emphasizes the structural features of the β subunits that enable new mechanisms of cofactor assembly and use of novel oxidants.